Tetracycline-Related Transcriptional Regulation of the CTnDOT Mobilization Region

Waters, Jillian L.; Wang, Guirong; Salyers, Abigail A.

doi:10.1128/jb.00691-13

Cited by 9 publications

(8 citation statements)

References 29 publications

(44 reference statements)

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“…This is due largely to a repressor of conjugative transfer, the small RNA RteR. In addition, we recently showed that the CTnDOT-encoded integrase, IntDOT, may also inhibit conjugative transfer (42, 43). An overview of the CTnDOT transcriptional cascade is shown in Fig.…”

Section: Ctndot Overviewmentioning

confidence: 99%

“…Sequential deletion analysis of the excision operon demonstrates that an in-frame deletion of either xis2d or exc is sufficient to diminish mob transcription to the constitutive levels, while a deletion of either xis2c or orf3 has no effect (43). While both the mob operon and tra operon share a requirement for xis2d to enhance transcription, they differ in that the mob operon also requires exc , and the tra operon requires xis2c in addition to xis2d (Fig.…”

Section: Ctndot Overviewmentioning

confidence: 99%

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Regulation of CTnDOT Conjugative Transfer Is a Complex and Highly Coordinated Series of Events

Waters

Salyers

2013

mBio

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CTnDOT is a 65-kb conjugative transposon that is found in Bacteroides spp., which are one of the more abundant members within the lower human gastrointestinal tract. CTnDOT encodes resistance to the antibiotics erythromycin and tetracycline (Tc). An interesting feature of CTnDOT is that exposure to low levels of Tc induces a cascade of events that ultimately results in CTnDOT conjugative transfer. However, Tc is apparently not a switch that activates transfer but rather a signal that appears to override a series of negative regulators that inhibit premature excision and transfer of CTnDOT. In this minireview, we summarize over 20 years of research that focused on elucidating the highly coordinated regulation of excision, mobilization, and transfer of CTnDOT.

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Section: Ctndot Overviewmentioning

confidence: 99%

Section: Ctndot Overviewmentioning

confidence: 99%

Regulation of CTnDOT Conjugative Transfer Is a Complex and Highly Coordinated Series of Events

Waters

Salyers

2013

mBio

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“…However, Xis2c and Xis 2d have also been identified as positive regulators of the tra genes that encode proteins involved in conjugation (6). In addition, Xis2d and Exc also appear to stimulate expression of the mob operon that encodes the relaxase and coupling proteins required for mobilization (7). CTnDOT also encodes two antibiotic resistance genes, tetQ and ermF (8, 9).…”

Section: Introductionmentioning

confidence: 99%

The Integration and Excision of CTnDOT

Wood

Gardner

2015

Microbiol Spectr

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Bacteroides species are one of the most prevalent groups of bacteria present in the human colon. Many strains carry large, integrated elements including integrative and conjugative elements (ICEs). One such ICE is CTnDOT, which is 65 kb in size and encodes resistances to tetracycline and erythromycin. CTnDOT has been increasing in prevalence in Bacteroides spp., and is now found in greater than 80% of natural isolates. In recent years, CTnDOT has been implicated in the spread of antibiotic resistance among gut microbiota. Interestingly, the excision and transfer of CTnDOT is stimulated in the presence of tetracycline. The tyrosine recombinase IntDOT catalyzes the integration and excision reactions of CTnDOT. Unlike the well-characterized lambda Int, IntDOT tolerates heterology in the overlap region between the sites of cleavage and strand exchange. IntDOT also appears to have a different arrangement of active site catalytic residues. It is missing one of the arginine residues that is conserved in other tyrosine recombinases. The excision reaction of CTnDOT is complex, involving excision proteins Xis2c, Xis2d, and Exc, as well as IntDOT and a Bacteroides host factor. Xis2c and Xis2d are small, basic proteins like other recombination directionality factors (RDFs). Exc is a topoisomerase; however, the topoisomerase function is not required for the excision reaction. Exc has been shown to stimulate excision frequencies when there are mismatches in the overlap regions, suggesting that it may play a role in resolving Holliday junctions containing heterology. Work is currently under way to elucidate the complex interactions involved with the formation of the CTnDOT excisive intasomes.

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“…Deletion of either orf3 or exc had no effect on the transcriptional regulation of the tra genes (16). Recent studies showed that Xis2d and Exc are responsible for positively regulating the transcription of the mob operon (18). The mob operon consists of three genes ( mobA - mobB - mobC ) that encode proteins in the relaxosome complex, which is responsible for transferring the CTnDOT DNA to the mating apparatus (18, 19).…”

Section: 1 Introductionmentioning

confidence: 99%

“…Recent studies showed that Xis2d and Exc are responsible for positively regulating the transcription of the mob operon (18). The mob operon consists of three genes ( mobA - mobB - mobC ) that encode proteins in the relaxosome complex, which is responsible for transferring the CTnDOT DNA to the mating apparatus (18, 19). Deletions of either xis2c or orf3 have no effect on the transcriptional regulation of the mob genes (18).…”

Section: 1 Introductionmentioning

confidence: 99%

The Xis2d protein of CTnDOT binds to the intergenic region between the mob and tra operons

Hopp

Gardner

Salyers

2015

Plasmid

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CTnDOT is a 65kbp integrative and conjugative element (ICE) that carries genes encoding both tetracycline and erythromycin resistances. The Excision operon of this element encodes Xis2c, Xis2d, and Exc proteins involved in the excision of CTnDOT from host chromosomes. These proteins are also required in the complex transcriptional regulation of the divergently transcribed transfer (tra) and mobilization (mob) operons of CTnDOT. Transcription of the tra operon is positively regulated by Xis2c and Xis2d, whereas, transcription of the mob operon is positively regulated by Xis2d and Exc. Xis2d is the only protein that is involved in the excision reaction, as well as the transcriptional regulation of both the mob and tra operons. This paper helps establish how Xis2d binds the DNA in the mob and tra region. Unlike other excisionase proteins, Xis2d binds a region of dyad symmetry. The binding site is located in the intergenic region between the mob and tra promoters, and once bound Xis2d induces a bend in the DNA. Xis2d binding to this region could be the preliminary step for the activation of both operons. Then the other proteins, like Exc, can interact with Xis2d and form higher order complexes.

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Tetracycline-Related Transcriptional Regulation of the CTnDOT Mobilization Region

Cited by 9 publications

References 29 publications

Regulation of CTnDOT Conjugative Transfer Is a Complex and Highly Coordinated Series of Events

Regulation of CTnDOT Conjugative Transfer Is a Complex and Highly Coordinated Series of Events

The Integration and Excision of CTnDOT

The Xis2d protein of CTnDOT binds to the intergenic region between the mob and tra operons

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